Aspirin (Includes Midol Traditional) ↔ coagulation

The use of aspirin is contraindicated in patients with significant active bleeding or hemorrhagic disorders such as hemophilia, von Willebrand's disease, or telangiectasia. Aspirin interferes with coagulation by irreversibly inhibiting platelet aggregation and prolonging bleeding time. The non-aceylated salicylates (i.e. salicylate salts such as sodium or magnesium salicylate) do not demonstrate these effects and may be appropriate substitutions in these patients. However, all salicylates can interfere with the action of vitamin K and induce a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX and X. At usual recommended dosages, a slight increase in prothrombin time (PT) may occur. Therapy with salicylates, especially aspirin, should be administered with extreme caution in patients with hypoprothrombinemia, vitamin K deficiency, thrombocytopenia, thrombotic thrombocytopenic purpura, severe hepatic impairment, or anticoagulant use.

CNS stimulants (Includes Midol Traditional) ↔ cardiac disease

The use of CNS stimulants is contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in adults and children taking CNS stimulant treatment. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

CNS stimulants (Includes Midol Traditional) ↔ hypertension

CNS stimulant medications have shown to increase blood pressure, and their use might be contraindicated in patients with severe hypertension. Caution should be used when administering to patients with preexisting high blood pressure and other cardiovascular conditions. All patients under treatment should be regularly monitored for changes in blood pressure and heart rate.

CNS stimulants (Includes Midol Traditional) ↔ liver disease

In general, CNS stimulants are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with CNS stimulants should be administered cautiously in patients with moderate to severe liver disease, and the dosage should be adjusted accordingly. Additionally, postmarketing reports have shown that atomoxetine can cause severe liver injury. Laboratory testing should be done at the first sign or symptom of liver dysfunction (jaundice, dark urine, upper quadrant tenderness) and treatment should be discontinued in patients with evidence of liver injury.

References

Methylxanthines (Includes Midol Traditional) ↔ PUD

Severe Potential Hazard, High plausibility. Applies to: Peptic Ulcer

Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

NSAIDs (Includes Midol Traditional) ↔ asthma

Severe Potential Hazard, High plausibility. Applies to: Asthma

Approximately 10% of patients with asthma may have aspirin-sensitive asthma, characterized by nasal polyposis, pansinusitis, eosinophilia, and precipitation of asthma and rhinitis attacks after ingestion of aspirin. The use of aspirin in these patients has been associated with severe bronchospasm and fatal anaphylactoid reactions. Since cross-sensitivity has been noted between aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), therapy with any NSAID should be avoided in asthmatic patients with a history of aspirin or other NSAID sensitivity, and administered cautiously in all patients with preexisting asthma. Prior to initiating therapy with NSAIDs, patients should be questioned about previous allergic-type reactions to these agents. Salicylate salts, salsalate, salicylamide, and acetaminophen may be appropriate alternatives in patients with a history of NSAID-induced bronchospasm, since cross-sensitivity to these agents appears to be low. However, cross-sensitivity has been demonstrated occasionally with high dosages of these agents (e.g., acetaminophen >= 1000 mg), thus it may be appropriate to initiate therapy with low dosages and increase gradually. There is some evidence suggesting that COX-2 inhibitors may be safely used in patients with aspirin-sensitive asthma, although the labeling for these products contraindicate such use. If necessary, aspirin desensitization may also be attempted in some patients under medical surveillance.

Salicylates, particularly aspirin, can cause dose-related gastrointestinal bleeding and mucosal damage, which may occur independently of each other. Occult, often asymptomatic GI blood loss is quite common with usual dosages of aspirin and stems from the drug's local effect on the GI mucosa. During chronic therapy, this type of bleeding may occasionally produce iron deficiency anemia. In contrast, major upper GI bleeding rarely occurs except in patients with active peptic ulcers or recent GI bleeding. However, these patients generally do not experience greater occult blood loss than healthy patients following small doses of aspirin. Mucosal damage associated with the use of salicylates may lead to development of peptic ulcers with or without bleeding, reactivation of latent ulcers, and ulcer perforation. Therapy with salicylates and related agents such as salicylamide should be considered and administered cautiously in patients with a history of GI disease or alcoholism, particularly if they are elderly and/or debilitated, since such patients may be more susceptible to the GI toxicity of these drugs and seem to tolerate ulceration and bleeding less well than other individuals. Extreme caution and thorough assessment of risks and benefits are warranted in patients with active or recent GI bleeding or lesions. Whenever possible, especially if prolonged use is anticipated, treatment with non-ulcerogenic agents should be attempted first. If salicylates are used, close monitoring for toxicity is recommended. Some adverse GI effects may be minimized by administration with high dosages of antacids, use of enteric-coated or extended-release formulations, and/or concurrent use of a histamine H2-receptor antagonist or a cytoprotective agent such as misoprostol. Patients with active peptic ulceration or GI bleeding treated with salicylates should generally be administered a concomitant anti-ulcer regimen.

Salicylates (Includes Midol Traditional) ↔ renal dysfunction

Salicylate and its metabolites are eliminated almost entirely by the kidney. Therapy with salicylate drugs should be administered cautiously in patients with renal impairment, especially if it is severe. Reduced dosages may be necessary to avoid drug accumulation. Clinical monitoring of renal function is recommended during prolonged therapy, since the use of salicylate drugs has rarely been associated with renal toxicities, including elevations in serum creatinine, renal papillary necrosis, and acute tubular necrosis with renal failure. Most of the data have been derived from experience with aspirin but may apply to other salicylates as well. In patients with impaired renal function, aspirin has caused reversible and sometimes marked decreases in renal blood flow and glomerular filtration rate. Adverse renal effects have usually reversed rapidly following withdrawal of aspirin therapy.

Salicylates (Includes Midol Traditional) ↔ Reye's syndrome

The use of salicylates, primarily aspirin, in children with varicella infections or influenza-like illnesses has been associated with an increased risk of Reye's syndrome. Although a causal relationship has not been established, the majority of evidence to date seems to support the association. Most authorities, including the American Academy of Pediatrics Committee on Infectious Diseases, recommend avoiding the use of salicylates in children and teenagers with known or suspected varicella or influenza and during presumed outbreaks of influenza. If antipyretic or analgesic therapy is indicated under these circumstances, acetaminophen may be an appropriate alternative. The same precautions should also be observed with related agents such as salicylamide or diflunisal because of their structural and pharmacological similarities to salicylate.

Caffeine (Includes Midol Traditional) ↔ cardiotoxicity

Like other methylxanthines, caffeine at high dosages may be associated with positive inotropic and chronotropic effects on the heart. Caffeine may also produce an increase in systemic vascular resistance, resulting in elevation of blood pressure. Therapy with products containing caffeine should be administered cautiously in patients with severe cardiac disease, hypertension, hyperthyroidism, or acute myocardial injury. Some clinicians recommend avoiding caffeine in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an acute myocardial infarction.

References

"Multum Information Services, Inc. Expert Review Panel"

Moderate

CNS stimulants (Includes Midol Traditional) ↔ psychiatric disorders

The use of CNS stimulants can cause psychotic or maniac symptoms, suicidal ideation, aggression and can exacerbate symptoms of behavior disturbance and thought disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders, and all patients should be monitored closely, specially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. All patients receiving treatment should be screened for bipolar disease prior to initiation. If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. CNS stimulants are contraindicated in patients with marked agitation or anxiety.

CNS stimulants (Includes Midol Traditional) ↔ renal dysfunction

Overall CNS stimulants should be administered with caution in patients with significantly impaired renal function as the reduction in the rate of elimination may alter the therapeutic response. The dosage should be adjusted accordingly.

CNS stimulants (Includes Midol Traditional) ↔ seizure disorders

Due to general central nervous system stimulation, therapy with CNS stimulant drugs may cause seizures. These drugs may lower the convulsive threshold in patients with prior history of seizures or EEG abnormalities, and very rarely in patients with no previous history of seizures. Therapy with CNS stimulants should be used with caution in patients with or predisposed to seizures. If seizures appear, therapy should be discontinued.

Methylxanthines (Includes Midol Traditional) ↔ GERD

Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

Salicylates (Includes Midol Traditional) ↔ anemia

Moderate Potential Hazard, Moderate plausibility. Applies to: Anemia

Occult, often asymptomatic GI blood loss occurs quite frequently with the use of normal dosages of aspirin and stems from the drug's local effect on the GI mucosa. During chronic therapy, this type of bleeding may occasionally produce iron deficiency anemia. Other salicylates reportedly cause little or no GI blood loss at usual dosages, but may do so at high dosages. Prolonged therapy with salicylates, particularly aspirin, should be administered cautiously in patients with or predisposed to anemia. Periodic monitoring of hematocrit is recommended. The same precautions should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate.

Salicylates (Includes Midol Traditional) ↔ dialysis

Salicylate and its metabolites are readily removed by hemodialysis and, to a lesser extent, by peritoneal dialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Salicylates (Includes Midol Traditional) ↔ G-6-PD deficiency

Salicylates, particularly aspirin, may cause or aggravate hemolysis in patients with pyruvate kinase or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. However, this effect has not been clearly established. Until more data are available, therapy with salicylates should be administered cautiously in patients with G-6-PD deficiency. The same precaution should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate.

Salicylates (Includes Midol Traditional) ↔ hepatotoxicity

The use of salicylates has occasionally been associated with acute, reversible hepatotoxicity, primarily manifested as elevations of serum transaminases, alkaline phosphatase and/or, rarely, bilirubin. Hepatic injury consistent with chronic active hepatitis has also been reported in a few patients, which resulted rarely in encephalopathy or death. Salicylate-induced hepatotoxicity appears to be dependent on serum salicylate concentration (> 25 mg/dL) and has occurred most frequently in patients with juvenile arthritis, active systemic lupus erythematosus, rheumatic fever, or preexisting hepatic impairment. Therapy with salicylates, particularly when given in high dosages, should be administered cautiously in these patients, and periodic monitoring of liver function is recommended. The same precautions should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate. A dosage reduction may be necessary if liver function abnormalities develop and serum salicylate concentration exceeds 25 mg/dL, although serum transaminase elevations may sometimes be transient and return to pretreatment values despite continued therapy without dosage adjustment.